CN101810878A - Nanofibrous Tubular Scaffolds with Hierarchical Porous Structure - Google Patents
Nanofibrous Tubular Scaffolds with Hierarchical Porous Structure Download PDFInfo
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- CN101810878A CN101810878A CN201010171672A CN201010171672A CN101810878A CN 101810878 A CN101810878 A CN 101810878A CN 201010171672 A CN201010171672 A CN 201010171672A CN 201010171672 A CN201010171672 A CN 201010171672A CN 101810878 A CN101810878 A CN 101810878A
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Abstract
本发明涉及一种具有多级孔结构的组织工程管状支架。支架具有至少一个的轴向排列的通道，通道的横截面面积为300μm2～300mm2，支架的非通道部分存在相互贯通的微孔，微孔的体积范围为1μm3～5000μm3，微孔孔径分布曲线呈锯齿状，支架微孔壁为纳米级纤维三维网络。同时，支架中含有改变细胞与组织的生理学行为功能的药物，在应用过程中，可向其所在环境按一定规律释放这些功能药物，药物种类、负载量和释放速率可根据实际需要进行设定。这种具有精细拓扑结构和生物学功能的组织工程支架，具有广阔的前景。
The invention relates to a tubular scaffold for tissue engineering with a multi-level hole structure. The scaffold has at least one channel arranged in the axial direction, the cross-sectional area of the channel is 300μm 2 ~ 300mm 2 , there are interpenetrating micropores in the non-channel part of the scaffold, the volume of the micropores ranges from 1μm 3 to 5000μm 3 , and the diameter of the micropores is The distribution curve is zigzag, and the micropore wall of the scaffold is a three-dimensional network of nanoscale fibers. At the same time, the stent contains drugs that change the physiological behavior and functions of cells and tissues. During the application process, these functional drugs can be released to the environment where they are located according to a certain rule. The drug type, loading and release rate can be set according to actual needs. This kind of tissue engineering scaffold with fine topological structure and biological function has broad prospects.
Description
Technical field
The present invention relates to a kind of tissue engineering tubular scaffold, particularly a kind of multichannel nanofiber medicine slow release stent with hierarchical porous structure.
Background technology
In recent years, organizational project has obtained development at full speed as a new technique of repair and reconstruction tissue.The tissue engineering tubular scaffold of the carrier of holder, cytokine and the function medicament of growing as cell and tissue growth in the tissue engineering technique evolution, has been subjected to the attention of researcher.Tissue engineering tubular scaffold is as the basis of tissue engineering technique, and its applied environment is quite complicated.Thereby, when design and preparation tissue engineering tubular scaffold, should consider, take into account various factors from a plurality of angles, could more adapt to complex environment, the repairing effect of obtaining, effectively avoid risk.
In organizational project scientific research at present and the clinical practice, employed support with nano-scale fiber three-dimensional network form, single and the inaccuracy of structural parameters and form, the passage that lacks variform and distribution, therefore the micropore that does not more have a plurality of size grades and variform can only obtain simple experimental result and limited clinical effectiveness.
On the other hand, many in the research of existing medicament slow release system and the application based on the microsphere of one-dimentional structure and the film of two-dimensional structure, do not see the three-dimensional medicine slow release stent model that has complex topology structure and medicine sustained release function concurrently.
Summary of the invention
The object of the present invention is to provide a kind of novel tissue engineering tubular scaffold.
The technical solution used in the present invention is:
A kind of tissue engineering tubular scaffold, support have the passage of the axially-aligned of at least one, and the cross-sectional area of passage is 300 μ m
2～300mm
2, there is the micropore that connects mutually in the non-channel part of support, and the volume range of micropore is 1 μ m
3～5000 μ m
3, micropore size distribution curve indentation, support micro-pore wall are the nano-scale fiber three-dimensional network.
Preferably, support is made by Biodegradable Polymers.
Preferably, be added with the medicine of physiology's behavior that can change cell and tissue in the support.
Tissue engineering tubular scaffold of the present invention has passage and fibrillar meshwork structure, the micropore that particularly in support, has particular design, thereby having higher porosity and permeability, this hierarchical porous structure more meets the cell growth promoter and organizes the demand that forms on form.
Tissue engineering tubular scaffold of the present invention is by load and sustained release to the Biofunctional medicine, improve the environment that cell is grown from chemistry and biological structure, by selection and setting to function medicament component and release thereof, can more effectively realize pair cell and tissue the physiology behavior control and induce, make the effect of support obtain tremendous increase.
This pore size distribution curve indentation, the rich and varied hierarchical porous structure of pore morphology, more help the accurate control that the support Chinese medicine discharges, make the mechanical property and the degraded character controllable adjustment scope of support more wide, thereby can obtain more excellent effect.
Description of drawings
Fig. 1 is passage in the tissue engineering tubular scaffold entity of the present invention and 30 * sem photograph of non-channel part;
Fig. 2 is 150 * sem photograph of the non-channel part cross section of tissue engineering tubular scaffold entity of the present invention;
Fig. 3 is 500 * sem photograph of the microcellular structure in the non-channel part of tissue engineering tubular scaffold entity of the present invention;
Fig. 4 is 5000 * sem photograph of the nano-scale fiber structure in the non-channel part of tissue engineering tubular scaffold entity of the present invention;
Fig. 5 is the GDNF and the bFGF release profiles of tissue engineering tubular scaffold of the present invention;
Fig. 6 is the pore size distribution curve of the hierarchical porous structure in the tissue engineering tubular scaffold of the present invention.
The specific embodiment
Below in conjunction with drawings and Examples, further specify the present invention.
A kind of tissue engineering tubular scaffold, support have the passage of the axially-aligned of at least one, and the cross-sectional area of passage is 300 μ m
2～300mm
2, there is the micropore that connects mutually in the non-channel part of support, and the volume range of micropore is 1 μ m
3～5000 μ m
3, micropore size distribution curve indentation, support micro-pore wall are the nano-scale fiber three-dimensional network.
Hierarchical porous structure refers to micropore size distribution curve indentation, and promptly the aperture of micropore non-single normal distribution in the successive range of regulation distributes but concentrate in the interval of the some or several non-overlapping copies in the scope of regulation.At nanometer, submicron, micron, millimeter---on the yardstick of different brackets, there are one or more peak values in the pore size distribution curve of micropore, and has certain spacing between peak and the peak, indentation, as shown in Figure 6.
Preferably, support is made by Biodegradable Polymers, Biodegradable Polymers comprises chitosan, cellulose, collagen, sericin, gelatin, hyaluronic acid, alginic acid and derivant thereof, by lactide, Acetic acid, hydroxy-, bimol. cyclic ester, caprolactone, the dioxy ring hexane ketone of mixing, carbonic ester, the ortho esters monomer, agate quinoline two one monomers, the malic acid internal ester monomer, the homopolymer of phosphate ester monomer preparation, random, block copolymer, polyurethane, polyethers, polyureas, poly 3-hydroxy butyrate, poly-3-hydroxyl valerate, and above-mentioned high molecular copolymer and blend.
Preferably, be added with the medicine of physiology's behavior that can change cell and tissue in the support, to improve the biological function of support.Medicine comprises function functional group, sequence and the fragment in immunosuppressant, low molecular weight heparin, anesthetis, somatomedin, cytoskeleton composition, regeneration promotion functional gene and corresponding source.
Tissue engineering tubular scaffold of the present invention by with the macromolecular material dissolution with solvents, injects the mould that contains porogen then, and solvent and porogen are removed in the typing back, can obtain by drying.
Number and the arrangement mode of tissue engineering tubular scaffold of the present invention because of having different passages, the channel cross-section of different shape, the micropore of non-channel part, support performance and applied environment produce and further expand.As improving as further, in the central shaft radiation direction of support, the interchannel distance of support changes in gradient, can make brace aperture rate and mechanical property have gradient character; And for example, as further improvement, the passage in the support has quincunx cross section, and perhaps the micropore in the support makes the structure of support be particularly suitable for some histiocytic growth for other forms except that spherical, cylindrical.
In the preparation process of support, can regulate affinity between drug molecule and the backing substrate material by the following parameter of control: (1) selects the macromolecule raw material of different component, molecular weight for use; (2) the pore size distribution curve form of the multistage microcellular structure of control; (3) mode of connection between selection drug molecule and the timbering material is as covalency link, physical absorption and hydrogen bond; (4) degradation rate of adjusting support.Use above means, can artificially set the release profiles of support Chinese medicine,, have the support that discharges the ability of multiple medicine along time shaft successively as making to satisfy the real needs of using.
Fig. 1～4 are the sem photograph of tissue engineering tubular scaffold typical model of the present invention, as can be seen from the figure, tissue engineering tubular scaffold of the present invention has clear and definite multilevel hierarchy, and layer of structure is clearly demarcated, have the different size grade, channel cross sectional area is at 300 μ m
2～300mm
2Between, the volume range of single micropore is at 1 μ m
3～5mm
3Between, the diameter of nano-scale fiber is between 10nm～1000nm.
Fig. 5 is GDNF and the bFGF release profiles in the tissue engineering tubular scaffold typical model of the present invention, as can be seen from the figure, the violent release phenomenon is not seen in two kinds of factor approximately linear releases in time in the 24d, tissue engineering tubular scaffold of the present invention has excellent drug and discharges the control function.
Use aperture and pore-size distribution in the mercury injection apparatus mensuration support, obtain the pore size distribution curve of the multistage microcellular structure in the tissue engineering tubular scaffold typical model of the present invention, as shown in Figure 6.As can be seen from the figure, the pore size distribution curve indentation of micropore, in pore diameter range 0.1 μ m～1000 mu m ranges, the aperture of all micropores is concentrated in 3 μ m～15 μ m intervals, 16 μ m～30 μ m interval and interval three intervals of 35 μ m～60 μ m and is distributed in the support.The structure of multistage micropore has crucial effects for whole mechanical property of support and degradation property.
In sum, tissue engineering tubular scaffold of the present invention is when having passage and fibrillar meshwork structure, have meticulous multistage microcellular structure, thereby possess higher porosity and better permeability, and hierarchical porous structure more meets the cell growth promoter and organizes the demand that forms on form.
Tissue engineering tubular scaffold of the present invention is by load and sustained release to the Biofunctional medicine, improve the environment that cell is grown from chemistry and biological structure, can more effectively realize pair cell and tissue the physiology behavior control and induce, make the effect of support obtain tremendous increase.
The existence of hierarchical porous structure and form more help the accurate control that the support Chinese medicine discharges, and make the mechanical property of support and degraded character controllable adjustment wider, thereby can obtain more excellent effect.
Claims (6)
1. tissue engineering tubular scaffold, it is characterized in that: described support has the passage of the axially-aligned of at least one, and the cross-sectional area of described passage is 300 μ m
2～300mm
2, there is the micropore that connects mutually in the non-channel part of support, and the volume range of micropore is 1 μ m
3～5000 μ m
3, micropore size distribution curve indentation, support micro-pore wall are the nano-scale fiber three-dimensional network.
2. tissue engineering tubular scaffold according to claim 1 is characterized in that: the diameter of described nano-scale fiber is 10nm～1000nm.
3. tissue engineering tubular scaffold according to claim 1 is characterized in that: described support is made by Biodegradable Polymers.
4. Biodegradable Polymers according to claim 3 comprises: chitosan, cellulose, collagen, sericin, gelatin, hyaluronic acid, alginic acid and derivant thereof, homopolymer, random, block copolymer by lactide, Acetic acid, hydroxy-, bimol. cyclic ester, caprolactone, the assorted hexane ketone of dioxy ring, carbonic ester, ortho esters monomer, agate quinoline two one monomers, malic acid internal ester monomer, phosphate ester monomer preparation, polyurethane, polyethers, polyureas, poly 3-hydroxy butyrate, poly-3-hydroxyl valerate, and above-mentioned high molecular copolymer and blend.
5. tissue engineering tubular scaffold according to claim 1 is characterized in that: described support is added with the medicine of physiology's behavior that can change cell and tissue.
6. tissue engineering tubular scaffold according to claim 5, it is characterized in that: the medicine that can change physiology's behavioral function of cell and tissue comprises: immunosuppressant, low molecular weight heparin, the functional group in somatomedin, extracellular matrix components, cytoskeleton composition, regeneration promotion functional gene and corresponding source, function sequence and fragment.
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| CN 201010171672 CN101810878B (en) | 2010-05-14 | 2010-05-14 | Nano-fiber tubular scaffold with multi-stage porous structure |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010171672 CN101810878B (en) | 2010-05-14 | 2010-05-14 | Nano-fiber tubular scaffold with multi-stage porous structure |
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| CN101810878B CN101810878B (en) | 2013-05-01 |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102813562A (en) * | 2011-06-10 | 2012-12-12 | 冯淑芹 | Three-dimensional large-aperture nanoscale fibrous scaffold and method for preparing same |
| CN102871772A (en) * | 2011-07-13 | 2013-01-16 | 冯淑芹 | Porous degradable blood vessel and preparation method thereof |
| CN103656758A (en) * | 2012-09-26 | 2014-03-26 | 中国科学院化学研究所 | Tissue engineering bracket imitating intima-media structure and function of natural blood vessels and preparation method thereof |
| CN104107097A (en) * | 2014-07-16 | 2014-10-22 | 上海交通大学 | Macroscopic-microcosmic-nanometer hierarchical mechanical compatible bone restoration and preparation thereof |
| CN105311683A (en) * | 2015-11-16 | 2016-02-10 | 清华大学 | Bionic tissue engineering scaffold containing inner channel network and oriented pore structure as well as preparation method and application of bionic tissue engineering scaffold |
| CN105499575A (en) * | 2015-12-20 | 2016-04-20 | 北京工业大学 | Design and manufacturing method of porous grid structure material |
| CN105589994A (en) * | 2015-12-20 | 2016-05-18 | 北京工业大学 | Topological optimization design method for porous material unit grid structure |
| CN106420125A (en) * | 2016-08-31 | 2017-02-22 | 广州新诚生物科技有限公司 | Tissue engineering scaffold for directional microchannel and preparation method of tissue engineering scaffold |
| CN108201632A (en) * | 2016-12-20 | 2018-06-26 | 重庆润泽医药有限公司 | A kind of articular cartilage repaiies scaffold |
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Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102813562A (en) * | 2011-06-10 | 2012-12-12 | 冯淑芹 | Three-dimensional large-aperture nanoscale fibrous scaffold and method for preparing same |
| CN102871772A (en) * | 2011-07-13 | 2013-01-16 | 冯淑芹 | Porous degradable blood vessel and preparation method thereof |
| CN103656758A (en) * | 2012-09-26 | 2014-03-26 | 中国科学院化学研究所 | Tissue engineering bracket imitating intima-media structure and function of natural blood vessels and preparation method thereof |
| CN103656758B (en) * | 2012-09-26 | 2014-12-10 | 中国科学院化学研究所 | Tissue engineering bracket imitating intima-media structure and function of natural blood vessels and preparation method thereof |
| CN104107097A (en) * | 2014-07-16 | 2014-10-22 | 上海交通大学 | Macroscopic-microcosmic-nanometer hierarchical mechanical compatible bone restoration and preparation thereof |
| CN105311683B (en) * | 2015-11-16 | 2019-01-04 | 清华大学 | A kind of network containing internal channel and the bionical tissue engineering bracket of directional pore structure and the preparation method and application thereof |
| CN105311683A (en) * | 2015-11-16 | 2016-02-10 | 清华大学 | Bionic tissue engineering scaffold containing inner channel network and oriented pore structure as well as preparation method and application of bionic tissue engineering scaffold |
| CN105499575A (en) * | 2015-12-20 | 2016-04-20 | 北京工业大学 | Design and manufacturing method of porous grid structure material |
| CN105499575B (en) * | 2015-12-20 | 2017-07-07 | 北京工业大学 | A kind of design and preparation method of perforated grill structural material |
| CN105589994B (en) * | 2015-12-20 | 2018-12-07 | 北京工业大学 | The method of topological optimization design of porous material unit grid structure |
| CN105589994A (en) * | 2015-12-20 | 2016-05-18 | 北京工业大学 | Topological optimization design method for porous material unit grid structure |
| CN106420125A (en) * | 2016-08-31 | 2017-02-22 | 广州新诚生物科技有限公司 | Tissue engineering scaffold for directional microchannel and preparation method of tissue engineering scaffold |
| CN106420125B (en) * | 2016-08-31 | 2018-06-22 | 广州新诚生物科技有限公司 | Orient the tissue engineering bracket preparation method of microchannel |
| CN108201632A (en) * | 2016-12-20 | 2018-06-26 | 重庆润泽医药有限公司 | A kind of articular cartilage repaiies scaffold |
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